Project Summary We propose to purchase a multispectral optoacoustic tomography (MSOT) system from iThera, a whole-body small animal optoacoustic imaging system with broad excitation capability from the visible to near infrared spectral range. Optoacoustic tomography is an exciting new technology that combines the high sensitivity of optical imaging with the depth sensitivity and resolution of ultrasonography for high-resolution imaging of soft tissue structures, endogenous chromophores, and exogenous optical contrast agents, without using ionizing radiation. A combination of multispectral laser excitation with a 270-degree coverage provides true multi-slice anatomic and contrast-enhanced images of small animals from head to tail. Differential absorption of light by endogenous hemoglobin-related biomolecules aids in delineating vascular structures from surrounding tissue in real time for monitoring angiogenesis in cardiovascular disease, cancer, and other diseases. The system also uses the ratio of oxy- and deoxyhemoglobin to enable functional neuroimaging, identify hypoxic conditions in cancer microenvironments, and track how pathophysiological processes mediate health and disease. Similarly, biosynthetic fluorescent proteins, synthetic dyes, and light-absorbing nanoparticles can serve as molecular probes for whole-body imaging of animal models of human diseases and quantitative monitoring of treatment response. This instrument, which will be part of the Washington University Molecular Imaging Center, will support 15 NIH-funded users from diverse research fields, enhancing their current research capabilities with non-invasive, longitudinal visualization of disease processes deep within living animals, and quantification of biological processes without euthanizing animals. Availability of this instrument to the NIH-funded researchers and many other minor users at Washington University will not only enhance their ongoing studies but also stimulate new discoveries in disease processes and the development of new diagnostic and therapeutic agents for diverse diseases. The MSOT system will be housed in the Washington Molecular Imaging Center, which supports the preclinical optical imaging needs of over 80 NIH-funded investigators at Washington University and the surrounding research community. Highly experienced personnel will manage this instrument, train new users and provide expertise for research design, data acquisition, processing, and analysis. Overall, this instrument will facilitate new discoveries in preclinical research for eventual translation to human subjects.